G0S2 ameliorates oxidized low-density lipoprotein-induced vascular endothelial cell injury by regulating mitochondrial apoptosis

Zenghui Liang; Wenjie Diao; Yiyao Jiang; Yanrong Zhang

doi:10.21037/atm-22-5618

G0S2 ameliorates oxidized low-density lipoprotein-induced vascular endothelial cell injury by regulating mitochondrial apoptosis

Ann Transl Med. 2022 Dec;10(24):1383. doi: 10.21037/atm-22-5618.

Authors

Zenghui Liang¹, Wenjie Diao², Yiyao Jiang², Yanrong Zhang¹

Affiliations

¹ Department of Vascular Surgery, the Third Hospital of Hebei Medical University, Shijiazhuang, China.
² Department of Cardiac Surgery, the First Affiliated Hospital of Bengbu Medical College, Bengbu, China.

Abstract

Background: Oxidative low-density lipoprotein (ox-LDL)-induced endothelial cell damage is a major risk factor for atherosclerosis and its related cardiovascular diseases. The G0/G1 switch gene 2 (G0S2) is a multifunctional protein which has been poorly studied in atherosclerosis.

Methods: In this study, ox-LDL was utilized to construct a human aortic endothelial cell (HAEC) injury model.

Results: It was found that ox-LDL impaired cell viability, augmented lactate dehydrogenase (LDH) release, and reduced G0S2 levels in HAECs in a dose-dependent manner. Further, G0S2 overexpression improved the viability and restrained apoptosis of HAECs treated by ox-LDL. Conversely, G0S2 depletion decreased the viability and aggravated apoptosis of HAECs treated by ox-LDL. At the molecular level, G0S2 overexpression significantly increased the secretion of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPH-Px), promoted intracellular reactive oxygen species (ROS) production and malondialdehyde (MDA) content in HAECs under either normal or ox-LDL conditions. Meanwhile, the ox-LDL-induced mitochondrial dysfunction, as demonstrated by decreased mitochondrial membrane potential, translocation of mitochondrial cytochrome c (Cyt-c) to the cytoplasm, and activation of caspase-3 and caspase-9, was significantly reversed by G0S2 overexpression. In addition, G0S2 overexpression promoted the activation of AMP-activated protein kinase (AMPK) and increased the expression of nuclear factor erythroid-2-related factor-2 (Nrf2), sirtuin 1 (SIRT1) and heme oxygenase 1 (HO-1) under normal and ox-LDL conditions.

Conclusions: This study demonstrated that G0S2 protects against ox-LDL-induced vascular endothelial cell injury by regulating oxidative damage and mitochondrial homeostasis and may be a promising target for the treatment of atherosclerosis.

Keywords: G0/G1 switch gene 2 (G0S2); Human aortic endothelial cells (HAECs); mitochondrial homeostasis; oxidative damage.